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Biomedical subjects

M O'Neill

Publications and source records attributed to M O'Neill.

At least 91 records · Page 5Linked to original sources

Inotropic and calcium kinetic effects of calcium channel agonist and antagonist in isolated cardiac myocytes from cardiomyopathic hamsters.

The mechanism by which heart cells of cardiomyopathic (CM) hamsters become calcium overloaded is not known. We examined the number of slow calcium channels, calcium uptake via slow calcium channels, calcium pool sizes, and the contractile response to Bay K 8644, verapamil, and nifedipine using isolated cardiac myocytes from 8-9-month-old CM hamsters (BIO 14.6) and age-matched normal controls. The number of dihydropyridine binding sites as assessed by specific binding of [3H]PN200-110 was similar in the two groups (control hearts: Bmax = 333 +/- 89 [mean +/- SD] fmol/mg; CM hearts: Bmax = 357 +/- 75 fmol/mg; n = 5 experiments, p = 0.6). Current density through L-type calcium channels was determined using the whole-cell clamp technique (at -50 mV holding potential and -10 mV test potential) and was the same in CM myocytes (17.8 +/- 1.5 [mean +/- SD] pA/pF) and control myocytes (18.6 +/- 2.1 pA/pF) (n = 5 experiments, p = 0.5). The current-voltage relation (test potentials varied from -40 to +50 mV) was also the same in CM and control cells, as was apparent threshold, peak current, and reversal potential. However, the initial rate of 45Ca influx as well as the size of the rapidly exchangeable calcium pool was significantly greater in myocytes obtained from CM than from normal hamsters. In both myocyte preparations, Bay K 8644 increased the rate of 45Ca uptake by 25% at 60 seconds; verapamil decreased 45Ca uptake at 60 seconds by 16% and 17% in normal and CM hamsters, respectively. A similar inhibitory effect was observed with nifedipine. The amplitude of cell motion in cells driven at 1.5 Hz as assessed by an optical-video system increased progressively with increasing concentrations of extracellular calcium or Bay K 8644 in cardiac myocytes from normal or CM hamsters. However, the concentration-effect curves for the two effectors were shifted to the left in CM cells compared with cells from normal hamsters. Both preparations demonstrated similar contractile responses to verapamil and nifedipine. These findings demonstrate that single enzymatically dissociated cardiac myocytes from CM hamsters have impaired contractile properties analogous to those seen in the intact heart and thus provide a useful experimental system in which to study underlying cellular mechanisms operative in this model of heart failure. Our results further indicate that calcium overload in CM hamster cardiac myocytes may not be due to increased calcium influx via dihydropyridine-sensitive calcium channels, as suggested previously, but rather to abnormalities of intracellular calcium homeostasis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Endothelin enhances the contractile responsiveness of adult rat ventricular myocytes to calcium by a pertussis toxin-sensitive pathway.

It has long been assumed that the primary influences regulating cardiac contractility are the extent of mechanical loading of muscle fibers and the activity of the autonomic nervous system. However, the vasoactive peptide endothelin, initially found in vascular endothelium, is among the most potent positively inotropic agents yet described in mammalian myocardium. In isolated adult rat ventricular cells, endothelin's action was slow in onset but very long lasting with an EC50 of 50 pM that approximates the reported KD of the peptide for its receptor in rat heart. When the calcium activity of the buffer superfusing isolated single fura-2-loaded myocytes paced at 1.5 Hz was varied from 0.1 to 0.9 mM [Ca2+]o, 100 pM endothelin increased contractile amplitude with no significant change in diastolic or systolic [Ca2+]i, thus appearing to sensitize the myofilaments to intracellular calcium. Pertussis toxin, or prior exposure to a beta-adrenergic agonist, reduced or abolished the increase in myocyte contractility induced by endothelin. This novel and potent pharmacologic action of endothelin points to the potential importance of local, paracrine factors, perhaps derived from microvascular endothelium or endocardium, in the control of the contractile function of the heart.

Animals↗

tctex-1: a candidate gene family for a mouse t complex sterility locus.

The t complex of the mouse has an important role in male germ cell development and function. Multiple mutations in the t complex interact to alter profoundly the transmission ratio of t complex-bearing sperm or to cause complete sterility or semisterility. We have isolated a multigene family, tctex-1, by screening a testicular cell cDNA library with two reciprocally subtracted testicular cDNA probes. The tctex-1 gene family produces an abundant, virtually germ cell-specific transcript that is 8-fold overexpressed in t homozygotes. The aberrant expression of tctex-1 is solely dependent on the t haplotype genes and occurs only in germ cells. The chromosomal location and pattern of expression of tctex-1 make it a candidate for involvement in male sterility.

Amino Acid Sequence↗

Length changes in dendritic networks of cerebellar Purkinje cells of old rats after chronic ethanol treatment.

Dendritic networks of cerebellar Purkinje neurons from aging ethanol-treated Fisher 344 rats were analyzed for metric changes in terminal and internal segments of the networks. Mean lengths of three categories of dendritic segments were determined. No significant metric changes in segment lengths were detectable immediately at the termination of 24 weeks of ethanol treatment, but significant changes were apparent after 8 weeks of recovery from ethanol treatment. Return to a diet of standard laboratory chow was associated with a period of dendritic extension in networks from pair-fed control rats but not in those from the ethanol-treated rats. The resulting significant differences in mean segment length were restricted to the paired terminal segments at the peripheral tips of the bifurcating networks. Unpaired terminal segments and internal segments of the networks showed no significant changes in length during the recovery period.

Age Factors↗

Imaging Barrett's oesophagus.

Eight patients who had Barrett's oesophagus confirmed by histology are presented. All had barium swallow examinations and technetium-99m sodium pertechnetate (99Tcm-pertechnetate) scintigraphy, the findings of which are reviewed and discussed. The most valuable diagnostic signs on barium swallow examination related to the site of the stricture and the presence of mucosal outpouchings. Scintigraphy was positive in all eight cases. Patients suspected of having Barrett's oesophagus on barium swallow examination should undergo scintigraphy. When the latter is positive, the endoscopist should be alerted to obtain biopsies not only at the site of stricture but serially as far as the gastrooesophageal junction.

Aged↗

Measurement of six enzymes with the Kodak DTSC Module, a physician's office analyzer.

We evaluated the performance of the Kodak DTSC Module for determination of alanine aminotransferase (ALT; EC 2.6.1.2), aspartate aminotransferase (2.5.1.2), alkaline phosphatase (3.1.3.1), creatine kinase (2.7.3.2), gamma-glutamyltransferase (2.3.2.2), and lactate dehydrogenase (1.1.1.27). The DTSC is a "special chemistry" accessory for the DT60 analyzer; the same multilayer film technology as that of the Ektachem 700 is used. The overall precision, assessed over a three-month period with two serum-based quality control materials, ranged from 2.2 to 8.0%. DTSC results for patients' specimens correlated well with those by the Technicon RA-1000 analyzer. The performance of the analyzer in linearity and interference studies was satisfactory for clinical use. The DTSC is simple to operate and has no technique-dependent step; it should be useful for the physician's office laboratory.

Alanine Transaminase↗

[Constraints imposed by political factors upon government intervention and health promotion].

In this article, Michel O'Neill, Ph. D., discusses the necessity of taking political factors into consideration when embarking on preventive programmes, regardless of the level in the community in which the intervention is to take place. When using the term, "political factors", the author is referring to the powers of influence which certain individuals or groups inevitably have over members of a community, regardless of its size. The influence is thus not necessarily linked to partisan politics but potentially has extensive implications for health promotion activities. After an introduction to the history of the development of a community health oriented system in Quebec, O'Neill presents four examples (at the local, regional, provincial, and federal levels) to introduce his analysis of political influence in community health and its implications in health promotion programmes. The marketing genius and tremendous budget of a multinational, American-based fast food corporation represents the political influence contrary of health promotion interests in two of the examples: competing with nutrition education efforts at a local level and "philanthropically" supporting curative efforts at a regional level. At a provincial level, the perpetual problem of tobacco corporations influencing elected officials in their social policies is presented while the aberration between rhetoric vis à vis policy and the reality of non-action is cited as political influence at a federal level. The examples cited are only four among "dozens and dozens" and serve as a reminder that health promotion professionals must take political influences into account if they wish to implement effective policies and programmes.(ABSTRACT TRUNCATED AT 250 WORDS)

Community Health Services↗

Increased activities of creatine kinase and lactate dehydrogenase isoenzymes in a patient with metastatic ovarian tumor.

A 50-year-old woman with metastatic rhabdomyosarcoma of the ovary had increased activities of creatine kinase (CK; EC 2.7.3.2), CK-MB isoenzyme, lactate dehydrogenase (LD; EC 1.1.1.27), and LD-2 isoenzyme in her serum. The isoenzyme activities did not show a pattern of increasing, then decreasing. Clinical findings, including electrocardiograms, did not support the diagnosis of myocardial infarction. We suggest that high activities of CK-MB and LD-2 in serum may serve as a marker of rhabdomyosarcoma.

Creatine Kinase↗

HLA-DR-positive cells in the human amniochorion.

Human amniochorion has been studied by indirect immunofluorescence using a monoclonal antibody to a monomorphic determinant of HLA-DR antigens. Positive staining was noted only on significant numbers of large cells with irregular cytoplasmic processes in the mesenchymal connective tissue layer of the membranes. These cells resemble the dendritic-type, strongly HLA-DR-positive cells described by Steinman [3] and may be particularly relevant in immunobiological events at this important materno-foetal interface.

Amnion↗

Degenerative changes and detection of plasminogen in fetal membranes that rupture prematurely.

Amniochorion obtained at caesarean section and vaginal delivery, at 34-36 weeks gestation and at term, have been studied by electron microscopy and immunofluorescence for evidence of amniotic epithelial degenerative changes and the presence of plasminogen. When delivery was by caesarean section between 34-36 weeks, electron microscopy revealed no degenerative changes in four cases, but in two cases they were widespread. All but one membrane obtained at term showed only minimal amniotic epithelial cell degenerative changes, but extensive change was seen when delivery was premature after premature membrane rupture. Plasminogen was seen in amniotic epithelium proportional to the degree of cell degeneration; it was absent from healthy membranes. These findings demonstrate that degenerative changes are extensively present in membranes that rupture prematurely, particularly before the onset of premature labour, and suggest a role for plasminogen in membrane rupture.

Epithelium↗

[Not Available].

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Canada↗

Evaluation of adjuvant postoperative radiotherapy for lung cancer.

One hundred eighteen patients with lung cancer were retrospectively analyzed to determine whether postoperative radiotherapy (RT) improves survival. Patterns of treatment failure and three year NED (no evidence of disease) survival rates were assessed according to extent of tumor spread, histology, and treatment method. Patients with hilar or mediastinal node metastases were at higher risk of local failure compared to those with negative nodes. Postoperative RT reduced local recurrence and improved 3 year survival among patients with positive nodes. However, postoperative RT did not improve survival among those with negative nodes. Our data indicated that patients with positive hilar or mediastinal nodes may require postoperative RT to improve survival.

Adenocarcinoma↗

Carcinoma of the lung: evaluation of histological grade and factors influencing prognosis.

The results in 96 patients with lung cancer who underwent lobectomy or pneumonectomy were analyzed. In reviewing the case histories of these patients, it became apparent that those with poorly differentiated tumor (grade 3) have an increased likelihood of positive lymph node metastases compared with those with well-differentiated (grade 1) or moderately differentiated (grade 2) tumor. Poor differentiation of the tumor, vascular invasion, and lymph node metastases appear to represent poor prognostic indices in patients undergoing operation. Compared with patients with grade 1 and grade 2 tumors, patients with a grade 3 adenocarcinoma had more local recurrences, while those with grade 3 squamous cell carcinoma had more distant metastases. The findings suggest that histological grading is an important adjunct to the clinical evaluation of and planning of treatment for patients with lung cancer.

Adenocarcinoma↗